In some cases, dentures are beneficial to the nutritional status, speech, appearance, and quality of life of patients who are missing some or even all of their teeth. However, colonization and biofilm formation of Candida alibicans on denture materials can lead to Candida-associated denture stomatitis (CADS), which is a non-specific inflammatory reaction to microbial antigens, toxins and enzymes that are produced by the colonizing microorganisms.
CADS is a common, recurring disease that affects up to 67% of denture wearers. Factors such as poor oral hygiene, high carbohydrate intake, reduced salivary flow, continuous denture wearing, ageing, malnutrition, immunosuppression, radiation therapy, diabetes mellitus, and possibly treatment with antibiotics are known to increase susceptibility to CADS. In healthy individuals, CADS can be readily controlled. However, for patients who are debilitated, immunocompromised or suffering from systemic diseases, CADS may become a chronic condition; further, the colonized Candida alibicans and other species can cause caries, root caries, periodontal diseases, oral and systemic (e.g., gastrointestinal and pleuropulmonary) infections, and even death.
Management of CADS includes denture cleaning and disinfection, appropriate denture wearing habits, use of tissue conditioners or soft liners, and topical or systemic antifungal therapy. However, none of these methods can completely prevent or eliminate Candida alibicans colonization and biofilm formation, and the reinfection rate is high, particularly in those who are immunocompromised or medically compromised.
Since CADS is closely associated with Candida alibicans colonization and biofilm formation, the use of antifungal dentures can be an attractive option to control the disease. The general principle for fabricating antifungal dentures is to impregnate denture materials with antifungal drugs that elute from the device and impair microbial growth. A high antifungal concentration is reached (at least initially) in the near vicinity of the denture surface, generally exceeding the minimum inhibition concentration (MIC) and fungicidal concentration (MFC) required for susceptible species. The effectiveness and safety of these antifungal dentures for short-term use (e.g., days to weeks) have been confirmed in a number of studies.
However, most of the current antifungal denture materials cannot control CADS for long durations. The major challenge for long-term use of antifungal dentures is the lack of strategies to incorporate enough antifungal drugs into the prostheses and control antifungal drug release rate. The simplest method is to directly add antifungal agents into denture materials. In this approach, however, drug content is generally low, primarily because high drug content could damage the physical properties of the dentures.
Further, because the drugs are simply dispersed in dentures and there are no specific interactions to “hold” them, antifungal agents are released rapidly, in the first several hours or days. To introduce specific interactions, new polymer materials bearing anionic functional groups in the side chains have been synthesized, and these can bind and then slowly release antifungal agents. This method reduces the release rate, but antifungal duration is not improved because of the low amount of antifungal drugs absorbed.
In addition to short antifungal durations, the pattern of release of antifungal drugs needs further optimization. Current systems release antifungal drugs at a decreasing rate over time, regardless of whether colonization or infections are present. If the prostheses could respond to the presence of microbes or infections and initiate or stop drug release accordingly, their effectiveness in controlling CADS would be significantly improved. Unfortunately, this has not been achieved in practice.
Moreover, while drug combination, drug change or drug rotation can be a powerful tool to enhance inhibitory potency and reduce microbial drug resistance in the treatment of fungal infections, this method has not been adopted in the development of antifungal dentures. Rather, current systems normally use one or two antifungal agents, and once the antifungal dentures are fabricated, the structures and quantities of antifungal agents in the dentures are fixed, and cannot be changed in real applications even if the disease/patient's conditions warrant such changes.